1. Field of the Invention
The present invention relates to compounds capable of suppressing the phosphate concentration of serum, and more particularly to compounds useful for the prevention and treatment of hyperphosphatemia.
2. Related Art
The phosphate concentration of serum is specified by balance between absorption of phosphate from the intestine, intracellular and bone accumulation, filtration into primitive urine in the kidney, and subsequent reabsorption in uriniferous tubules. When the phosphate concentration of serum is not less than 5.0 mg/dl, this condition is called hyperphosphatemia and is a clinical condition that significantly appears mainly in end-stage renal failure and dialysis patients. This is mainly induced by deteriorated excretion of phosphate involved in elimination of renal function. It is also suggested that an increase in phosphate absorption from the intestine derived from the administration of vitamin D participates in this clinical condition. The hyperphosphatemia secondarily leads to hypocalcemia and thus induces secondary hyperparathyroidism which is in turn a principal factor for renal osteodystrophy.
In the prior art technique, to alleviate these clinical conditions, ingestion of a diet having a low phosphate content and the use of a phosphate adsorbent having the function of adsorbing phosphate in the diet have been carried out from the viewpoint of reducing the absorption of phosphate from the intestine. However, it has been pointed out that the diet having a low phosphate content is disadvantageous in that a nutritional disorder is likely to occur, for example, due to lack of ingestion of other nutriments, or observance of this dietary is difficult because the taste is not good. Representative examples of oral phosphate adsorbents include calcium preparations, magnesium preparations, and aluminum preparations. However, it has been pointed out, for example, that the calcium preparations and the magnesium preparations induce hypercalcemia and hypermagnesemia, respectively, and the aluminum preparations induce aluminum osteopathy, aluminum cerebropathy, and dialysis dementia. In recent years, various anion exchange resins have been developed as the oral phosphate adsorbent. Since, however, these anion exchange resins have lower phosphate adsorption capacity than the above group of compounds, a high level of dosage is necessary for phosphate absorption reduction purposes. Therefore, it cannot be said that the compliance for patients is good.
Despite the fact that all the conventional therapeutic agents for hyperphosphatemia suffer from the above problems, up to now, therapeutic agents for hyperphosphatemia which can solve the above problems have not been reported.
Therapeutic agents for hyperphosphatemia are disclosed, for example, in WO 98/03185 and Kidney and Metabolic Bone Diseases, Vol. 15, No. 1 pp 75-80 (2002).